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A case is presented in which diffuse lymphangiomatosis resulted in the complete loss of the maxillary dentoalveolar complex and underlying basal bone. The complex investigation and treatment of this patient over a 10-year period is presented, and the importance of a multidisciplinary team approach in providing a functional and esthetic rehabilitation is highlighted. The use of a vascularized bone graft based on the deep circumflex iliac artery and subsequent restoration with an implant-supported prosthesis is described. [ABSTRACT FROM AUTHOR]

Background: Increasing consumer reliance on prenatal multivitamins and minerals (PMVMs) underscores the importance of ensuring their quality and safety. Adequate choline and iodine intakes during pregnancy are crucial for fetal development, yet discrepancies between labeled and actual content in PMVM products pose significant health risks. Additionally, the potential presence of toxic heavy metals, such as arsenic, lead, and cadmium, raises concerns about potential adverse health effects., Objectives: This study aimed to valuate nonprescription and prescription PMVMs regarding choline and iodine content, as well as arsenic, lead, and cadmium., Methods: This observational study evaluated a convenience sample of nonprescription and prescription PMVM products from online retailers and local retail pharmacies. Products were analyzed using liquid chromatography mass spectrometry for choline and inductively coupled plasma mass spectrometry for iodine, arsenic, lead, and cadmium. Choline and iodine actual amounts were compared with reported label amounts and contaminant amounts were compared with United States Pharmacopeia (USP) standards., Results: In total, 32 nonprescription and 15 prescription PMVM products were analyzed. Choline amounts were reported on 12 of the 47 (25.6%) products, including 5 (41.7%) within 20% of the claimed amount, 2 (16.7%) over the claimed amount by >20%, and 5 (41.7%) under the claimed amount by >20%. Iodine amounts were reported on 25 of the 47 (53.2%) products, including 4 (16.0%) within 20% of the claimed amount, 20 (80.0%) under the claimed amount by >20%, and 1 (4.0%) over the claimed amount by >20%. Amounts of arsenic, lead, and cadmium above USP purity limits were found in 7 (14.9%), 2 (4.3%) and 13 (27.7%) PMVMs, respectively., Conclusions: Current PMVM labels are misleading with the potential to harm pregnant persons and fetuses through omission or inaccurate content of essential nutrients and inclusion of heavy metals. Regulation is needed, and the Food and Drug Administration needs sufficient authority and staffing to oversee these dietary supplements., Competing Interests: Conflict of interest LMB reports financial support from the Center for Science in the Public Interest. All other authors report no conflicts of interest., (Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Background: Exposure to extreme heat impacts millions of people worldwide and outdoor workers are among the populations most affected by hot temperatures. Heat stress induces several biological responses in humans, including the production of heat shock proteins (HSP) and antibodies against HSP (anti-HSP) which may play a central role in the body's cellular response to a hot environment., Objective: This longitudinal study investigated the impact of elevated temperatures and humidity on the presence of HSP70 and anti-HSP70 and examined relationships with markers of kidney function in an at-risk workforce under conditions of extreme heat and exertion in Guatemala., Methods: We collected ambient temperature and relative humidity data as well as biomarkers and clinical data from 40 sugarcane workers at the start and the end of a 6-month harvest. We used generalized mixed-effects models to estimate temperature effects on HSP70 and anti-HSP70 levels. In addition, we examined trends between HSP70 and anti-HSP70 levels and markers of kidney function across the harvest., Results: At the end of the harvest, temperatures were higher, and workers had, on average, higher levels of HSP70 and anti-HSP70 compared to the beginning of the season. We observed significant increasing trends with temperature indices, heat index, and HSP70 levels. Maximum temperature was associated with HSP70 increments after controlling for age, systolic and diastolic blood pressure (β: 0.21, 95% Confidence Interval: 0.09, 0.33). Kidney function decline across the harvest was associated with both higher levels of anti-HSP70 levels at the end of the harvest as well as greater increases in anti-HSP70 levels across the harvest., Conclusions: These results suggest that workplace heat exposure may increase the production of HSP70 and anti-HSP70 levels and that there may be a relationship between increasing anti-HSP70 antibodies and the development of renal injury. HSP70 holds promise as a biomarker of heat stress in exposed populations., (© 2024. The Author(s).)

With chronic disease prevalence on the rise globally, surveillance and monitoring are critical to improving health outcomes. Point-of-care (POC) testing can facilitate epidemiological research and enhance surveillance systems in limited resource settings, but previous research has identified bias between POC devices and laboratory testing. We compared the performance of two POC blood analyzers, the iSTAT handheld (Abbott, Princeton, NJ, USA) and the StatSensor Creatinine (Nova Biomedical, Waltham, MA, USA) to concurrent blood samples analyzed at a local laboratory that were collected from 89 agricultural workers in Guatemala. We measured creatinine and other measures of underlying health status with the POC and the lab blood samples. Pearson correlation coefficients, Bland-Altman plots, no intercept linear regression models and two-sample t-tests were used to evaluate the agreement between the POC and lab values collected across three study days and to assess differences by study day in a field setting. On average there was no observed difference between the iSTAT and lab creatinine measurements (p = 0.91), regardless of study day. Using lab creatinine as the gold standard, iSTAT creatinine results were more accurate compared to the Statsensor, which showed some bias, especially at higher values. The iSTAT had good agreement with the lab for sodium and blood urea nitrogen (BUN), but showed differences for potassium, anion gap, bicarbonate (TCO2), glucose, and hematocrit. In this tropical field setting, the research team devised a protocol to prevent the devices from overheating. In limited resource settings, POC devices carry advantages compared to traditional lab analyses, providing timely results to patients, researchers, and healthcare systems to better evaluate chronic health conditions. Technical challenges due to use of POC devices in high heat and humidity environments can be addressed using a standard protocol for transporting and operating the devices., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Krisher et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Neuroinflammation plays a crucial role in the development of neurodegenerative protein misfolding disorders. This category of progressive diseases includes, but is not limited to, Alzheimer's disease, Parkinson's disease, and prion diseases. Shared pathogenesis involves the accumulation of misfolded proteins, chronic neuroinflammation, and synaptic dysfunction, ultimately leading to irreversible neuronal loss, measurable cognitive deficits, and death. Presently, there are few to no effective treatments to halt the advancement of neurodegenerative diseases. We hypothesized that directly targeting neuroinflammation by downregulating the transcription factor, NF-κB, and the inflammasome protein, NLRP3, would be neuroprotective. To achieve this, we used a cocktail of RNA targeting therapeutics (SB_NI_112) shown to be brain-penetrant, nontoxic, and effective inhibitors of both NF-κB and NLRP3. We utilized a mouse-adapted prion strain as a model for neurodegenerative diseases to assess the aggregation of misfolded proteins, glial inflammation, neuronal loss, cognitive deficits, and lifespan. Prion-diseased mice were treated either intraperitoneally or intranasally with SB_NI_112. Behavioral and cognitive deficits were significantly protected by this combination of NF-κB and NLRP3 downregulators. Treatment reduced glial inflammation, protected against neuronal loss, prevented spongiotic change, rescued cognitive deficits, and significantly lengthened the lifespan of prion-diseased mice. We have identified a nontoxic, systemic pharmacologic that downregulates NF-κB and NLRP3, prevents neuronal death, and slows the progression of neurodegenerative diseases. Though mouse models do not always predict human patient success and the study was limited due to sample size and number of dosing methods utilized, these findings serve as a proof of principle for continued translation of the therapeutic SB_NI_112 for prion disease and other neurodegenerative diseases. Based on the success in a murine prion model, we will continue testing SB_NI_112 in a variety of neurodegenerative disease models, including Alzheimer's disease and Parkinson's disease.

Immune malfunction or misrecognition of healthy cells and tissue, termed autoimmune disease, is implicated in more than 80 disease conditions and multiple other secondary pathologies. While pan-immunosuppressive therapies like steroids can offer limited relief for systemic inflammation for some organs, many patients never achieve remission, and such drugs do not cross the blood-brain barrier, making them ineffective for tackling neuroinflammation. Especially in the brain, unintended activation of microglia and astrocytes is hypothesized to be directly or indirectly responsible for multiple sclerosis, amyotrophic lateral sclerosis, Parkinson's disease, and Alzheimer's disease. Recent studies have also shown that targeting inflammasomes and specific immune targets can be beneficial for these diseases. Furthermore, our previous studies have shown targeting NF-κB and NLRP3 through brain penetrant Nanoligomer cocktail SB_NI_112 (abbreviated as NI112) can be therapeutic for several neurodegenerative diseases. Here, we show safety-toxicity studies, followed by pharmacokinetics and biodistribution in small- (mice) and large-animal (dog) studies of this inflammasome-targeting Nanoligomer cocktail NI112. We conducted studies using four different routes of administration: intravenous, subcutaneous, intraperitoneal, and intranasal, and identified the drug concentration over time using inductively coupled plasma mass spectrometry in the blood serum, the brain (including different brain regions), and other target organs such as liver, kidney, and colon. Our results indicate that the Nanoligomer cocktail has a strong safety profile and shows high biodistribution ( F ∼ 0.98) and delivery across multiple routes of administration. Further analysis showed high brain bioavailability with a ratio of NI112 in brain tissue to blood serum of ∼30%. Our model accurately shows dose scaling, translation between different routes of administration, and interspecies scaling. These results provide an excellent platform for human clinical translation and prediction of therapeutic dosage between different routes of administration., Competing Interests: The authors declare the following competing financial interest(s): S.S., V.G., A.C., and P.N. work at Sachi Bio, a for-profit company, where the Nanoligomer technology was developed. A.C. and P.N. are the founders of Sachi Bio, and P.N. has filed a patent on this technology. Other authors declare no competing interest., (© 2024 American Chemical Society.)

While originally identified as an antiviral pathway, recent work has implicated that cyclic GMP-AMP-synthase-Stimulator of Interferon Genes (cGAS-STING) signaling is playing a critical role in the neuroinflammatory response to traumatic brain injury (TBI). STING activation results in a robust inflammatory response characterized by the production of inflammatory cytokines called interferons, as well as hundreds of interferon stimulated genes (ISGs). Global knock-out (KO) mice inhibiting this pathway display neuroprotection with evidence that this pathway is active days after injury; yet, the early neuroinflammatory events stimulated by STING signaling remain understudied. Furthermore, the source of STING signaling during brain injury is unknown. Using a murine controlled cortical impact (CCI) model of TBI, we investigated the peripheral immune and microglial response to injury utilizing male chimeric and conditional STING KO animals, respectively. We demonstrate that peripheral and microglial STING signaling contribute to negative outcomes in cortical lesion volume, cell death, and functional outcomes postinjury. A reduction in overall peripheral immune cell and neutrophil infiltration at the injury site is STING dependent in these models at 24 h. Transcriptomic analysis at 2 h, when STING is active, reveals that microglia drive an early, distinct transcriptional program to elicit proinflammatory genes including interleukin 1-β (IL-1β), which is lost in conditional knock-out mice. The upregulation of alternative innate immune pathways also occurs after injury in these animals, which supports a complex relationship between brain-resident and peripheral immune cells to coordinate the proinflammatory response and immune cell influx to damaged tissue after injury., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 the authors.)

Introduction: Sugarcane workers are exposed to potentially hazardous agrochemicals, including pesticides, heavy metals, and silica. Such occupational exposures present health risks and have been implicated in a high rate of kidney disease seen in these workers., Methods: To investigate potential biomarkers and mechanisms that could explain chronic kidney disease (CKD) among this worker population, paired urine samples were collected from sugarcane cutters at the beginning and end of a harvest season in Guatemala. Workers were then separated into 2 groups, namely those with or without kidney function decline (KFD) across the harvest season. Urine samples from these 2 groups underwent elemental analysis and untargeted metabolomics., Results: Urine profiles demonstrated increases in silicon, certain pesticides, and phosphorus levels in all workers, whereas heavy metals remained low. The KFD group had a reduction in estimated glomerular filtration rate (eGFR) across the harvest season; however, kidney injury marker 1 did not significantly change. Cross-harvest metabolomic analysis found trends of fatty acid accumulation, perturbed amino acid metabolism, presence of pesticides, and other known signs of impaired kidney function., Conclusion: Silica and certain pesticides were significantly elevated in the urine of sugarcane workers with or without KFD. Future work should determine whether long-term occupational exposure to silica and pesticides across multiple seasons contributes to CKD in these workers. Overall, these results confirmed that multiple exposures are occurring in sugarcane workers and may provide insight into early warning signs of kidney injury and may help explain the increased incidence of CKD among agricultural workers., (© 2024 International Society of Nephrology. Published by Elsevier Inc.)

Background. Silica nanoparticles found in sugarcane ash have been postulated to be a toxicant contributing to chronic kidney disease of unknown etiology (CKDu). However, while the administration of manufactured silica nanoparticles is known to cause chronic tubulointerstitial disease in rats, the effect of administering sugarcane ash on kidney pathology remains unknown. Here we investigate whether sugarcane ash can induce CKD in rats. Methods . Sugarcane ash was administered for 13 weeks into the nares of rats (5 mg/day for 5d/week), and blood, urine and kidney tissues were collected at 13 weeks (at the end of ash administration) and in a separate group of rats at 24 weeks (11 weeks after stopping ash administration). Kidney histology was evaluated, and inflammation and fibrosis (collagen deposition) measured. Results . Sugarcane ash exposure led to the accumulation of silica in the kidneys, lungs, liver and spleen of rats. Mild proteinuria developed although renal function was largely maintained. However, biopsies showed focal glomeruli with segmental glomerulosclerosis, and tubulointerstitial inflammation and fibrosis that tended to worsen even after the ash administration had been stopped. Staining for the lysosomal marker, LAMP-1, showed decreased staining in ash administered rats consistent with lysosomal activation. Conclusion . Sugarcane ash containing silica nanoparticles can cause CKD in rats.

Cancer treatment is one of the major health problems that burden our society. According to the American Cancer Society, over 1.9 million new cancer cases and ∼0.6 million deaths from cancer are expected in the US in 2023. Therapeutic targeting is considered to be the gold standard in cancer treatment. However, when a tumor grows beyond a critical size, its vascular system differentiates abnormally and erratically, creating a heterogeneous endothelial barrier that further restricts drug delivery into tumors. While several methods exist, these prompt tumor migration and the appearance of new metastatic sites. Herein, we propose an innovative method based on magneto-mechanical actuation (MMA) to induce endothelial permeability. This method employs FDA-approved PEGylated superparamagnetic iron oxide nanoparticles (PEG-SPIONs) and alternating nonheating magnetic fields. MMA lies in the translation of magnetic forces into mechanical agitation. As a proof of concept, we developed a 2D cell culture model based on human umbilical vein endothelial cells (HUVEC), which were incubated with PEG-SPIONs and then exposed to different magnetic doses. After adjusting the particle concentration, incubation times, and parameters (amplitude, frequency, and exposure time) of the magnetic field generator, we induced actin filament remodeling and subsequent vascular endothelial-cadherin junction disruption. This led to transient gaps in cell monolayers, through which fluorescein isothiocyanate-dextran was translocated. We observed no cell viability reduction for 3 h of particle incubation up to a concentration of 100 μg/mL in the presence and absence of magnetic fields. For optimal permeability studies, the magnetic field parameters were adjusted to 100 mT, 65 Hz, and 30 min in a pulse mode with 5 min OFF intervals. We found that the endothelial permeability reached the highest value (33%) when 2 h postmagnetic field treatment was used. To explain these findings, a magneto-mechanical transduced stress mechanism mediated by intracellular forces was proposed. This method can open new avenues for targeted drug delivery into anatomic regions within the body for a broad range of disease interventions.

SARS-CoV-2 causes the severe respiratory disease COVID-19. Remdesivir (RDV) was the first fast-tracked FDA approved treatment drug for COVID-19. RDV acts as an antiviral ribonucleoside (adenosine) analogue that becomes active once it accumulates intracellularly. It then diffuses into the host cell and terminates viral RNA transcription. Previous studies have shown that certain nucleoside analogues unintentionally inhibit mitochondrial RNA or DNA polymerases or cause mutational changes to mitochondrial DNA (mtDNA). These past findings on the mitochondrial toxicity of ribonucleoside analogues motivated us to investigate what effects RDV may have on mitochondrial function. Using in vitro and in vivo rodent models treated with RDV, we observed increases in mtDNA copy number in Mv1Lu cells (35.26% increase ± 11.33%) and liver (100.27% increase ± 32.73%) upon treatment. However, these increases only resulted in mild changes to mitochondrial function. Surprisingly, skeletal muscle and heart were extremely resistant to RDV treatment, tissues that have preferentially been affected by other nucleoside analogues. Although our data suggest that RDV does not greatly impact mitochondrial function, these data are insightful for the treatment of RDV for individuals with mitochondrial disease., (© 2023. Springer Nature Limited.)

Progressive massive pulmonary fibrosis among coal miners has unexpectedly increased. It would likely due to the greater generation of smaller rock and coal particles produced by powerful equipment used in modern mines. There is limited understanding of the relationship between micro- or nanoparticles with pulmonary toxicity. This study aims to determine whether the size and chemical characteristics of typical coal-mining dust contribute to cellular toxicity. Size range, surface features, morphology, and elemental composition of coal and rock dust from modern mines were characterized. Human macrophages and bronchial tracheal epithelial cells were exposed to mining dust of three sub- micrometer and micrometer size ranges at varying concentrations, then assessed for cell viability and inflammatory cytokine expression. Coal had smaller hydrodynamic size (180-3000 nm) compared to rock (495-2160 nm) in their separated size fractions, more hydrophobicity, less surface charge, and consisted of more known toxic trace elements (Si, Pt, Fe, Al, Co). Larger particle size had a negative association with in-vitro toxicity in macrophages (p < 0.05). Fine particle fraction, approximately 200 nm for coal and 500 nm for rock particles, explicitly induced stronger inflammatory reactions than their coarser counterparts. Future work will study additional toxicity endpoints to further elucidate the molecular mechanism causing pulmonary toxicity and determine a dose-response curve., (© 2023. The Author(s).)

As the world braces to enter its fourth year of the coronavirus disease 2019 (COVID-19) pandemic, the need for accessible and effective antiviral therapeutics continues to be felt globally. The recent surge of Omicron variant cases has demonstrated that vaccination and prevention alone cannot quell the spread of highly transmissible variants. A safe and nontoxic therapeutic with an adaptable design to respond to the emergence of new variants is critical for transitioning to the treatment of COVID-19 as an endemic disease. Here, we present a novel compound, called SBCoV202, that specifically and tightly binds the translation initiation site of RNA-dependent RNA polymerase within the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome, inhibiting viral replication. SBCoV202 is a Nanoligomer, a molecule that includes peptide nucleic acid sequences capable of binding viral RNA with single-base-pair specificity to accurately target the viral genome. The compound has been shown to be safe and nontoxic in mice, with favorable biodistribution, and has shown efficacy against SARS-CoV-2 in vitro . Safety and biodistribution were assessed using three separate administration methods, namely, intranasal, intravenous, and intraperitoneal. Safety studies showed the Nanoligomer caused no outward distress, immunogenicity, or organ tissue damage, measured through observation of behavior and body weight, serum levels of cytokines, and histopathology of fixed tissue, respectively. SBCoV202 was evenly biodistributed throughout the body, with most tissues measuring Nanoligomer concentrations well above the compound K D of 3.37 nM. In addition to favorable availability to organs such as the lungs, lymph nodes, liver, and spleen, the compound circulated through the blood and was rapidly cleared through the renal and urinary systems. The favorable biodistribution and lack of immunogenicity and toxicity set Nanoligomers apart from other antisense therapies, while the adaptability of the nucleic acid sequence of Nanoligomers provides a defense against future emergence of drug resistance, making these molecules an attractive potential treatment for COVID-19.

Objective: The aim of this in-vitro study was to compare the amount of material (post and luting agent) and root dentine removed using two methods for removal of endodontic posts., Methods: Human premolar teeth (n=20) were sectioned at the CEJ and fibre reinforced posts were cemented at a length of 10mm following root canal therapy. Teeth were randomly assigned to two study groups. The methods of removal compared were: the use of RTD re-access kit (Composipost, RTD, France, St Egreve) in a conventional hand-piece driven by an electric motor (Group A); or a long tapered diamond bur (FG Diamond grit bur, Dentsply Ltd, UK) in an air-driven high speed turbine (Group B). Using micro- CT the volume of material and root dentine removed for each sample was calculated., Results: Both the volume of material removed and the volume of root dentine removed were significantly greater when using diamond burs. (p⟨0.001). The volume of dentine removed using the diamond bur method (mean 22.64mm³) was greater than the volume removed using the reaccess kit (mean 11.71mm³)., Significance: Use of a diamond bur to remove fibre reinforced endodontic post removal poses higher risk for root perforation compared to the reaccess kit., (Copyright© 2022 Dennis Barber Ltd.)

The devastating effects of the coronavirus disease 2019 (COVID-19) pandemic have made clear a global necessity for antiviral strategies. Most fatalities associated with infection from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) result at least partially from uncontrolled host immune response. Here, we use an antisense compound targeting a previously identified microRNA (miRNA) linked to severe cases of COVID-19. The compound binds specifically to the miRNA in question, miR-2392, which is produced by human cells in several disease states. The safety and biodistribution of this compound were tested in a mouse model via intranasal, intraperitoneal, and intravenous administration. The compound did not cause any toxic responses in mice based on measured parameters, including body weight, serum biomarkers for inflammation, and organ histopathology. No immunogenicity from the compound was observed with any administration route. Intranasal administration resulted in excellent and rapid biodistribution to the lungs, the main site of infection for SARS-CoV-2. Pharmacokinetic and biodistribution studies reveal delivery to different organs, including lungs, liver, kidneys, and spleen. The compound was largely cleared through the kidneys and excreted via the urine, with no accumulation observed in first-pass organs. The compound is concluded to be a safe potential antiviral treatment for COVID-19.

Background: Per- and polyfluoroalkyl substances (PFASs) are widespread and persistent environmental contaminants. Exposure to several PFASs has been associated with altered immune function in humans, including autoimmune disease and impaired response to vaccination. However, changes to the profile of inflammatory biomarkers in adults exposed to PFASs has not been extensively described., Objective: To estimate cross-sectional associations between serum PFASs and markers of inflammation among adults in a population exposed to aqueous film forming foam (AFFF)-contaminated drinking water., Methods: We quantified concentrations of 48 PFASs in non-fasting serum samples from 212 non-smoking adults. In the same serum samples, we measured concentrations of ten pro- and anti-inflammatory cytokines. We restricted analysis to seven PFASs detected in >85% of participants and the following four cytokines detected in ≥30% of participants: interleukin [IL]-1β, IL-6, IL-10, and tumor necrosis factor [TNF]-α. We fit multiple linear regression or logistic regression models, adjusted for potential confounders, to estimate associations between concentrations of each PFAS and either continuous or categorical (above vs below limit of detection) concentrations of each cytokine. We additionally applied Bayesian kernel machine regression to describe the combined effect of the PFAS mixture on each cytokine outcome., Results: Certain PFAS concentrations in this sample were elevated compared to a US nationally representative sample; median levels of PFHxS, ΣPFOS and ΣPFOA in this sample were 13.8, 2.1 and 1.7 times higher, respectively, than medians observed in the U.S., Sample: Higher concentrations of multiple PFASs were significantly associated with lower odds of detectable IL-1β. Weaker associations were observed with other cytokines. In general, perfluoroalkyl carboxylic acids had inverse associations with TNF-α, whereas the perfluoroalkyl sulfonic acids showed positive associations., Conclusions: We observed preliminary evidence of altered inflammatory profiles among adults with elevated serum concentrations of PFASs due to contaminated drinking water. Modifications to inflammatory pathways may be one mechanism by which PFAS exposures produce adverse health effects in humans, but this finding requires verification in longitudinal studies as well as phenotypic anchoring to immune function outcomes., (Copyright © 2021 Elsevier GmbH. All rights reserved.)

Objectives: There is a lack of information on cotinine levels in rural populations in low-income and middle-income countries like Guatemala. Therefore, there is a need to explore smoking status and biomarkers of tobacco use in epidemiological research in rural, low-income populations, in particular those at-risk for chronic kidney disease of unknown origin (CKDu)., Design: We evaluated self-reported smoking status against urinary cotinine levels, the gold standard biomarker of tobacco smoke exposure, among agricultural workers at four separate cross-sectional time points., Setting: Guatemala., Participants: 283 sugarcane workers., Primary Outcome Measures: Compared self-reported smoking status and urinary cotinine levels in two agricultural worker studies., Results: Self-reported smoking prevalence was 12% among workers. According to cotinine levels (≥50 ng/mL), the smoking prevalence was 34%. Self-reported smoking status had 28% sensitivity and 96% specificity. Urinary cotinine levels show that smoking prevalence is underestimated in this worker population., Conclusions: According to our findings, smoking status should be objectively measured with biomarkers rather than self-reported in CKDu epidemiological research. Self-reported smoking status is likely an underestimate of the true smoking prevalence among agricultural workers. Research on the CKDu epidemic in Central America and other parts of the world might be underestimating tobacco exposure as a potential contributor to the development of CKDu., Competing Interests: Competing interests: University of Colorado and Pantaleon are separate, independent organisations. University of Colorado employed appropriate research methods in keeping with academic freedom, based conclusions on critical analysis of the evidence and reported findings fully and objectively. The terms of this arrangement have been reviewed and approved by the University of Colorado in accordance with its conflict of interest policies., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Vasopressin is elevated in response to heat and dehydration and has been postulated to have a role in the chronic kidney disease of unknown origin being observed in Central America. The aims of this study were to examine whether the vasopressin pathway, as measured by copeptin, is associated with the presence of kidney dysfunction, and to examine whether higher fluid intake is associated with lower circulating copeptin and thereby preserves kidney health among sugarcane workers exposed to hot conditions., Methods: Utilizing a longitudinal study of 105 workers in Guatemala, we examined relationships between hydration indices, plasma copeptin concentrations, and kidney function markers at 3 times during the 6-month harvest. We also examined whether baseline copeptin concentrations increased the odds of developing an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2., Results: Copeptin concentrations were positively associated with serum creatinine (β 1.41, 95% CI 0.88-2.03) and negatively associated with eGFR (β -1.07, 95% CI -1.43 to -0.70). In addition, as workers improved their hydration (measured by increases in fluid balance), copeptin concentrations were reduced, and this reduction was associated with an improvement in kidney function., Conclusions: Results suggest that copeptin should be studied as a potential prognostic biomarker., (© 2020 S. Karger AG, Basel.)

Unconventional oil and gas development (UOGD) in the United States is increasingly being conducted on multiwell pads (MWPs) and in residential areas. We measured air pollution, noise, and truck traffic during four distinct phases of UOGD: drilling, hydraulic fracturing, flowback, and production. We monitored particulate matter (PM 2.5 ), black carbon (BC), A-weighted (dBA), and C-weighted (dBC) noise using real-time instruments on 1 and 5 min time scales, and truck traffic for 4-7 days per phase at a large 22-well pad sited in a residential area of Weld County, Colorado. Hydraulic fracturing, which requires frequent truck trips to move supplies and diesel engines to power the process, had the highest median air pollution levels of PM 2.5 and BC and experienced the greatest number of heavy trucks per hour compared to other phases. Median air pollution was lowest during drilling at this MWP, possibly because an electric drill rig was used. The equivalent continuous noise level ( L eq ) exceeded guidelines of 50 dBA and 65 dBC for A-weighted and C-weighted noise, respectively, during all development phases. Our data show that these multiple stressors are present around the clock at these sites, and this work provides baseline measurements on likely human exposure levels near similarly sized MWPs.

Background: Oil and natural gas (O&G) extraction emits pollutants that are associated with cardiovascular disease, the leading cause of mortality in the United States., Objective: We evaluated associations between intensity of O&G activity and cardiovascular disease indicators., Methods: Between October 2015 and May 2016, we conducted a cross-sectional study of 97 adults living in Northeastern Colorado. For each participant, we collected 1-3 measurements of augmentation index, systolic and diastolic blood pressure (SBP and DBP), and plasma concentrations of interleukin (IL)- 1β, IL-6, IL-8 and tumor necrosis factor alpha (TNF-α). We modelled the intensity of O&G activity by weighting O&G well counts within 16 km of a participant's home by intensity and distance. We used linear models accounting for repeated measures within person to evaluate associations., Results: Adjusted mean augmentation index differed by 6.0% (95% CI: 0.6, 11.4%) and 5.1% (95%CI: -0.1, 10.4%) between high and medium, respectively, and low exposure tertiles. The greatest mean IL-1β, and α-TNF plasma concentrations were observed for participants in the highest exposure tertile. IL-6 and IL-8 results were consistent with a null result. For participants not taking prescription medications, the adjusted mean SBP differed by 6 and 1 mm Hg (95% CIs: 0.1, 13 mm Hg and -6, 8 mm Hg) between the high and medium, respectively, and low exposure tertiles. DBP results were similar. For participants taking prescription medications, SBP and DBP results were consistent with a null result., Conclusions: Despite limitations, our results support associations between O&G activity and augmentation index, SBP, DBP, IL-1β, and TNF-α. Our study was not able to elucidate possible mechanisms or environmental stressors, such as air pollution and noise., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Exposure to an outgroup member voicing criticism of his or her own group fosters greater openness to the outgroup's perspective. Research suggests that this effect owes its influence to a serial process in which participants' perception of the risk involved in voicing internal criticism leads to an increase in the perceived credibility of the speaker. The credibility makes it possible for the speaker to be viewed as open-minded, which subsequently inspires greater hope. This process culminates in an increased openness to the outgroup. These findings have been restricted to the Israeli-Palestinian conflict, but here we examine their generalizability to racial conflict in the United States. Results reveal that White Americans exposed to internal criticism expressed by a Black authority figure express greater openness to African-American perspectives on race relations and are more willing to support policies of racial equality. Replicating past research, this effect is serially mediated by risk, credibility, and hope.

Public concern about oil and gas (O&G) operations in residential areas is substantial. Noise from construction and drilling related to O&G operations may be greater than other phases of O&G operations; yet the impacts of audible and low-frequency noise during these operations are not extensively explored nor the effects on health well understood. This study documents the noise levels at a multi-well O&G well pad during construction and drilling in a residential area in Colorado. A-weighted (dBA) and C-weighted (dBC) noise measurements were collected at four locations during development over a 3-month period. The maximum 1-min equivalent continuous sound levels over a 1-month period were 60.2 dBA and 80.0 dBC. Overall, 41.1% of daytime and 23.6% of nighttime dBA 1-min equivalent continuous noise measurements were found to exceed 50 dBA, and 97.5% of daytime and 98.3% of nighttime measurements were found to exceed 60 dBC. Noise levels exceeding 50 dBA or 60 dBC may cause annoyance and be detrimental to health; thus, these noise levels have the potential to impact health and noise levels and associated health effects warrant further investigation.

Environmental noise from sources such as traffic, airports, and oil and gas (O&G) operations is associated with nuisance and health concerns. Smartphones with external microphones have been recommended for environmental noise monitoring and may be useful tools for citizen science, but are not validated against reference methods. We evaluated laboratory performance of three smartphone/application (app) configurations recommended for environmental noise measurement. Two smartphone/app configurations were also compared to a reference sampler, a type 1 sound level meter (SLM) at ten outdoor sites with traffic, airport, and O&G noise. To evaluate performance, we compared the mean squared error, variance, bias, and Krippendorff's Alpha by smartphone/app combination and testing location for both audible (A-weighted) and low-frequency (C-weighted) noise. We observed that laboratory measurements were in strong agreement with a reference sampler. The field A-weighted noise level results had strong agreement with the SLM at several outdoor sites, but our C-weighted noise results ranged from moderate to substantial agreement. For our tested configurations, we find that smartphones with external microphones are reliable proxies for measuring A- and C-weighted noise in a laboratory setting. Outdoor performance depends on noise source type, weighting, and precision and accuracy needs of the investigation.

Research suggests that hearing an outgroup member voice internal criticism increases individuals' openness to the outgroup's perspective. We replicate and extend these findings in the context of the Israeli-Palestinian conflict. Israeli participants exposed to a Palestinian official voicing internal criticism reported more openness to the Palestinian narrative of the conflict, an effect that was mediated by an increase in participants' perception that Palestinians are open-minded and a subsequent increase in their hope for more positive relations between the two groups. In our extension of these findings, we examined a complementary mechanism contributing to the effectiveness of the criticism manipulation, specifically the extent to which participants perceive that the Palestinian official took a risk voicing criticism of Palestinians. Positive messages from a hostile outgroup may be received with suspicion, but if they are articulated under great risk to the speaker, greater credibility may be granted. Across two studies, we demonstrate that the criticism conveys risk to the speaker and that this risk is predictive of the perceived credibility of the speaker, and participants' subsequent openness to the outgroup's perspective., (© 2017 The British Psychological Society.)

Background: Roofers are at increased risk for various malignancies and their occupational exposures to polycyclic aromatic hydrocarbons (PAHs) have been considered as important risk factors. The overall goal of this project was to investigate the usefulness of phosphorylated histone H2AX (γH2AX) as a short-term biomarker of DNA damage among roofers., Methods: Blood, urine, and dermal wipe samples were collected from 20 roofers who work with hot asphalt before and after 6 h of work on Monday and Thursday of the same week (4 sampling periods). Particle-bound and gas-phase PAHs were collected using personal monitors during work hours. γH2AX was quantified in peripheral lymphocytes using flow cytometry and 8-hydroxy-2-deoxyguanosine (8-OHdG) was assessed in urine using ELISA. General linear mixed models were used to evaluate associations between DNA damage and possible predictors (such as sampling period, exposure levels, work- and life-style factors). Differences in mean biomarker and DNA damage levels were tested via ANOVA contrasts., Results: Exposure measurements did not show an association with any of the urinary biomarkers or the measures of DNA damage. Naphthalene was the most abundant PAH in gas-phase, while benzo(e)pyrene was the most abundant particle-bound PAH. Post-shift levels of γH2AX and 8-OHdG were higher on both study days, when compared to pre-shift levels. Cigarette smoking was a predictor of γH2AX and urinary creatinine was a predictor of urinary 8-OHdG. Between-subject variance to total variance ratio was 35.3 % for γH2ax and 4.8 % for 8-OHdG., Conclusion: γH2AX is a promising biomarker of DNA damage in occupational epidemiology studies. It has a lower within-subject variation than urinary 8-OHdG and can easily be detected in large scale groups. Future studies that explore the kinetics of H2AX phosphorylation in relation to chemical exposures may reveal the transient and persistent nature of this sensitive biomarker of early DNA damage.

Background: Osteoarthritis of the trapeziometacarpal joint of thumb occurs frequently and can be very disabling. Numerous surgical techniques including trapeziectomy with or without tendon interposition arthrodesis and partial or total joint arthroplasty with cemented and noncemented prosthesis have been described for the treatment of trapeziometacarpal joint osteoarthritis. Initial problems of osteolysis and implant loosening have been substantially reduced with improvement in implant design. The aim of this study is to demonstrate that trapeziometacarpal osteoarthritis of the thumb can be effectively treated with uncemented total joint replacement prosthesis., Materials and Methods: We retrospectively collected data for 16 trapeziometacarpal joint replacements in 14 patients. One patient was excluded as they required revision with trapeziectomy and ligament reconstruction following fracture of Trapezium. The trapeziometacarpal joint prosthesis was used in all cases and all operations were carried out by one surgeon. Clinical outcome was determined by a pre and postoperative patient rated wrist evaluation (PRWE) and Michigan Hand Questionnaire Score. Range of motion, grip, tip pinch and key pinch strength were measured and compared with the unoperated hand. Radiological assessment was carried out by plain radiographs for preoperative staging of arthritis and postoperative radiographs at latest followup for evaluation of osteolysis and implant loosening. Average followup period was 26 months., Results: There was an improvement in hand function and pain level based on PRWE and Mischigan Hand outcome Questionnaire Score. One patient had intraoperative fracture of Trapezium and subsequent radiographs at 14 months followup showed loosening of the trapezial component due to nonunion of the fracture and complete disintegration of the trapezium. There were no cases of dislocation or implant loosening for the remaining 15 CMC joints at the latest followup., Conclusion: The use of uncemented prosthesis in treatment of Questionnaire Score. Range of motion joint osteoarthritis gives excellent short term results in improving hand function in terms of strength and stability and achieving pain relief.

Cretaceous ichthyosaurs have typically been considered a small, homogeneous assemblage sharing a common Late Jurassic ancestor. Their low diversity and disparity have been interpreted as indicative of a decline leading to their Cenomanian extinction. We describe the first post-Triassic ichthyosaur from the Middle East, Malawania anachronus gen. et sp. nov. from the Early Cretaceous of Iraq, and re-evaluate the evolutionary history of parvipelvian ichthyosaurs via phylogenetic and cladogenesis rate analyses. Malawania represents a basal grade in thunnosaurian evolution that arose during a major Late Triassic radiation event and was previously thought to have gone extinct during the Early Jurassic. Its pectoral morphology appears surprisingly archaic, retaining a forefin architecture similar to that of its Early Jurassic relatives. After the initial latest Triassic radiation of early thunnosaurians, two subsequent large radiations produced lineages with Cretaceous representatives, but the radiation events themselves are pre-Cretaceous. Cretaceous ichthyosaurs therefore include distantly related lineages, with contrasting evolutionary histories, and appear more diverse and disparate than previously supposed.

Although researchers have investigated power relationships in families for twenty-five years, conclusions about normative family power patterns have been inconsistent and contradictory. Comparisons across studies have been difficult owing to different definitions of the construct, multiple methodologies, and inconsistent goals. With such confusion, a new, more integrated theoretical approach to the power issue seems warranted, as is suggested by the present paper. The current individual focus on power as a personal attribute can be replaced by a more dynamic, reciprocal, interactive process. Instead of specific or stable power patterns, power interactions should be fluid and time- or situation- specific. No one member would dominate, since power involves a mutual relationship system that changes its content, though not its rules of operation, across decision-making areas. Furthermore, family adjustment would relate to those rules and the family members' reactions to their particular exchange system but not to specific types of power structures. With these considerations, future research should analyze the process, not the content, of power operations in order to maximize the clinical and theoretical utility of its construct.